Fiche publication


Date publication

août 2019

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Pr VIGNAUD Jean-Michel


Tous les auteurs :
Alcala N, Leblay N, Gabriel AAG, Mangiante L, Hervas D, Giffon T, Sertier AS, Ferrari A, Derks J, Ghantous A, Delhomme TM, Chabrier A, Cuenin C, Abedi-Ardekani B, Boland A, Olaso R, Meyer V, Altmuller J, Le Calvez-Kelm F, Durand G, Voegele C, Boyault S, Moonen L, Lemaitre N, Lorimier P, Toffart AC, Soltermann A, Clement JH, Saenger J, Field JK, Brevet M, Blanc-Fournier C, Galateau-Salle F, Le Stang N, Russell PA, Wright G, Sozzi G, Pastorino U, Lacomme S, Vignaud JM, Hofman V, Hofman P, Brustugun OT, Lund-Iversen M, Thomas de Montpreville V, Muscarella LA, Graziano P, Popper H, Stojsic J, Deleuze JF, Herceg Z, Viari A, Nuernberg P, Pelosi G, Dingemans AMC, Milione M, Roz L, Brcic L, Volante M, Papotti MG, Caux C, Sandoval J, Hernandez-Vargas H, Brambilla E, Speel EJM, Girard N, Lantuejoul S, McKay JD, Foll M, Fernandez-Cuesta L

Résumé

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

Référence

Nat Commun. 2019 Aug 20;10(1):3407